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Self-assembled NIR-II Fluorophores with Ultralong Blood Circulation for Cancer Imaging and Image-guided Surgery
Journal of Medicinal Chemistry ( IF 7.3 ) Pub Date : 2021-12-24 , DOI: 10.1021/acs.jmedchem.1c01615
Yang Li 1, 2, 3 , Jianfeng Gao 1, 4 , Shuping Wang 5 , Mingxia Du 1 , Xiaowen Hou 1 , Tian Tian 2 , Xue Qiao 2 , Zhiquan Tian 2 , Peter J Stang 6 , Shijun Li 5 , Xuechuan Hong 1, 2 , Yuling Xiao 1, 2, 3
Affiliation  

Complete excision of the last remaining 1–2% of tumor tissue without collateral damage remains particularly challenging. Herein, we report thiophenthiadiazole (TTD)-derived fluorophores L6-PEGnk (n = 1, 2, 5) as new-generation NIR-II (1000–1700 nm) probes with exceptional nonfouling performance and significantly high fluorescence quantum yields in water. L6-PEG2k can self-assemble into vesicular micelles and exhibited minimal immunogenicity, low binding affinities, ultralong blood circulation (t1/2 = 59.5 h), and a supercontrast ratio in vivo. Most importantly, L6-PEG2k achieved excellent in vivo CT-26 and U87MG tumor targeting and accumulation (>20 d) through intraperitoneal or intravenous injection. A subcutaneous U87MG tumor and orthotopic brain glioma were successfully resected under NIR-II FIGS in our animal model via intraperitoneal injection in an extended time window (48–144 h). This study highlights the potential of using L6-PEG2K as self-assembling molecular probes with long-circulation persistence for routine preoperative tumor assessment and precise intraoperative image-guided resection.

中文翻译:

用于癌症成像和图像引导手术的具有超长血液循环的自组装 NIR-II 荧光团

在没有附带损伤的情况下完全切除最后剩余的 1-2% 的肿瘤组织仍然特别具有挑战性。在这里,我们报告了噻吩噻二唑 (TTD) 衍生的荧光团L6-PEG nk ( n = 1, 2, 5) 作为新一代 NIR-II (1000-1700 nm) 探针,在水中具有出色的防污性能和显着高的荧光量子产率. L6-PEG 2k可以自组装成囊泡胶束,在体内表现出最小的免疫原性、低结合亲和力、超长的血液循环( t 1/2 = 59.5 h)和超对比度。最重要的是,L6-PEG 2k在体内取得了优异的成绩CT-26 和 U87MG 通过腹膜内或静脉内注射靶向和积聚(>20 天)。在我们的动物模型中,通过腹膜内注射在延长的时间窗口(48-144 小时)内成功切除了皮下 U87MG 肿瘤和原位脑胶质瘤。本研究强调了使用L6-PEG 2K作为具有长循环持久性的自组装分子探针用于常规术前肿瘤评估和精确术中图像引导切除的潜力。
更新日期:2022-02-10
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